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| ID | Type | Description | Link |
|---|---|---|---|
| OCEANMIST | Other Identifier | Alias Study Number |
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This study aims to compare real-world effectiveness of BRAF/MEK inhibitors in BRAF-mutant metastatic melanoma patients in the United States by line of therapy.
The Flatiron Health electronic health record (EHR) data from US cancer clinics will be used for this retrospective database analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Encorafenib + binimetinib | Encorafenib 450 mg once a day (QD) Binimetinib 45 mg twice a day (BID) |
| |
| Vemurafenib + Cobimetinib | Vemurafenib 960 mg twice a day (BID) for 28 days of 28 day cycle Cobimetinib 60 mg once a day (QD) for 21 days of 28 day cycle |
| |
| Dabrafenib + trametinib | Dabrafenib 150 mg twice a day (BID) Trametinib 2 mg once a day (QD) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Encorafenib | Drug | 450 mg QD |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | As per COLUMBUS trial, OS was defined as the time from the date of randomization to the date of death due to any cause; if death was not observed, participants were censored at the date of last contact or the data analysis cut-off date, whichever occurred first. As per Flatiron EHR, OS was defined as the time from the index date to the date of death; participants without a date of death were censored at their last known activity date or the end of the follow-up period, whichever occurred first. Index date in each treatment group was defined as the date of treatment initiation. Kaplan-Meier analyses was used for analysis. | COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months) |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | COLUMBUS:PFS=time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurred first; PD:at least 20 percentage (%) increase in the sum of diameter of all measured target lesions, reference to the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter square (mm2) or the appearance of 1 or more new lesion, if a participant did not have an event at the analysis cut-off date, PFS was censored at the date of the last adequate tumour assessment. Flatiron:PFS=time from the index date to either the date of first PD event or death in the absence of progression; participants without PD or death were censored at the last date the participant could have been assessed for progression or the data analysis cut-off date, whichever occurred first. Index date was =the date of treatment initiation. |
Inclusion Criteria:
Exclusion Criteria:
-• Patients with prior BRAF- or MEK-inhibitor therapy
• Patients with ECOG performance status ≥ 2 (at the time of randomization for patients from COLUMBUS, during the baseline period for patients in Flatiron EHR)
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The study population will be metastatic melanoma patients receiving targeted combination therapies derived from an anonymized Flatiron Health data combined with patient data from COLUMBUS trial data
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | New York | New York | 10017 | United States |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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Data sources: COLUMBUS trial from 30-Dec-2013-15-Sept-2020 [approximately 80.5 months] and Flatiron Health electronic health Records (EHR) real-world database (RWD) from duration of 09-Jan-2014-30-Sep-2021 [92.7 months]. Planned cohorts in this study: 1) ENCO+BINI, pooled across COLUMBUS and Flatiron EHR; 2) DAB+TRAM: from Flatiron EHR; 3) VEM+COBI: from Flatiron EHR. Available retrospective data was evaluated in this observational study from 17-Jan-2022-31-Dec-2023 (approximately 23.5 months).
Data of eligible participants with v-Raf murine sarcoma viral oncogene homolog B protein (BRAF)V-600 mutant melanoma who aged greater than or equal to 18 years at the time of initiating treatment with encorafenib plus binimetinib (ENCO+BINI) or dabrafenib plus trametinib (DAB+TRAM) or vemurafenib plus cobimetinib (VEM+COBI) was collected retrospectively.
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| ID | Title | Description |
|---|---|---|
| FG000 | Encorafenib+Binimetinib | Participants with BRAFV600-mutant metastatic melanoma, who were enrolled between 30-December 2013 to 15-September-2020 in phase 3 COLUMBUS trial and eligible participants from RWD cohort identified from Flatiron Health Database between 27-June-2018 to 30-September- 2021 and treated with Encorafenib 450 mg once daily (QD) and Binimetinib 45 mg twice daily (BID)(ENCO+BINI) were included. |
| FG001 | Dabrafenib+Trametinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 09-January-2014 to 30-September-2021 and treated with Dabrafenib 150 mg BID+ Trametinib 2 mg QD (DAB+TRAM) were included. |
| FG002 | Vemurafenib + Cobimetinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 10-November-2015 to 30-September-2021 and treated with Vemurafenib 960 mg BID+ Cobimetinib 60 mg QD (VEM+COBI) were included. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Eligible participants whose data was retrieved and observed in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Encorafenib+Binimetinib | Participants with BRAFV600-mutant metastatic melanoma, who were enrolled between 30-December 2013 to 15-September-2020 in phase 3 COLUMBUS trial and eligible participants from RWD cohort identified from Flatiron Health Database between 27-June-2018 to 30-September- 2021 and treated with Encorafenib 450 mg QD and Binimetinib 45 mg BID (ENCO+BINI) were included. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Survival (OS) | As per COLUMBUS trial, OS was defined as the time from the date of randomization to the date of death due to any cause; if death was not observed, participants were censored at the date of last contact or the data analysis cut-off date, whichever occurred first. As per Flatiron EHR, OS was defined as the time from the index date to the date of death; participants without a date of death were censored at their last known activity date or the end of the follow-up period, whichever occurred first. Index date in each treatment group was defined as the date of treatment initiation. Kaplan-Meier analyses was used for analysis. | Analysis population included all eligible participants whose data were retrieved and observed in this study. | Posted | Median | 95% Confidence Interval | Months | COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months) |
|
All-cause mortality: COLUMBUS trial from 30-December-2013 to 15-September-2020 [approximately 80.5 months] and Flatiron EHR RWD from duration of 09-January-2014 to 30-September-2021 [92.7 months]; For adverse events it was not applicable as adverse event data was not planned to be collected.
This study is retrospective, it involves data that exist as structured data by the time of study start. The minimum criteria for reporting an adverse event (AE) (i.e., identifiable participant, identifiable reporter, a suspect product, and event) cannot be met. Hence, adverse events were not planned to be collected and are not reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Encorafenib+Binimetinib | Participants with BRAFV600-mutant metastatic melanoma, who were enrolled between 30-December 2013 to 15-September-2020 in phase 3 COLUMBUS trial and eligible participants from RWD cohort identified from Flatiron Health Database between 27-June-2018 to 30-September- 2021 and treated with Encorafenib 450 mg QD and Binimetinib 45 mg BID (ENCO+BINI) were included. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 19, 2023 | Dec 17, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 19, 2023 | Dec 17, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000601108 | encorafenib |
| D004333 | Drug Administration Routes |
| C581313 | binimetinib |
| D000077484 | Vemurafenib |
| C574276 | cobimetinib |
| C561627 | dabrafenib |
| C560077 | trametinib |
| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 |
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| Binimetinib | Drug | 45 mg BID |
|
|
| Vemurafenib | Drug | 960 mg BID for 28 days/cycle |
|
|
| Cobimetinib | Drug | 60 mg QD for 21 days/cycle |
|
|
| Dabrafenib | Drug | 150 mg BID |
|
|
| Trametinib | Drug | 2 mg QD |
|
|
| COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months) |
| BG001 | Dabrafenib+Trametinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 09-January-2014 to 30-September-2021 and treated with Dabrafenib 150 mg BID+ Trametinib 2 mg QD (DAB+TRAM) were included. |
| BG002 | Vemurafenib + Cobimetinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 10-November-2015 to 30-September-2021 and treated with Vemurafenib 960 mg BID+ Cobimetinib 60 mg QD (VEM+COBI) were included. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Dabrafenib+Trametinib |
Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 09-January-2014 to 30-September-2021 and treated with Dabrafenib 150 mg BID+ Trametinib 2 mg QD (DAB+TRAM) were included. |
| OG001 | Vemurafenib + Cobimetinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 10-November-2015 to 30-September-2021 and treated with Vemurafenib 960 mg BID+ Cobimetinib 60 mg QD (VEM+COBI) were included. |
| OG002 | Encorafenib+Binimetinib | Participants with BRAFV600-mutant metastatic melanoma, who were enrolled between 30-December 2013 to 15-September-2020 in phase 3 COLUMBUS trial and eligible participants from RWD cohort identified from Flatiron Health Database between 27-June-2018 to 30-September- 2021 and treated with Encorafenib 450 mg QD and Binimetinib 45 mg BID (ENCO+BINI) were included. |
|
|
|
| Other Pre-specified | Progression Free Survival (PFS) | COLUMBUS:PFS=time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurred first; PD:at least 20 percentage (%) increase in the sum of diameter of all measured target lesions, reference to the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter square (mm2) or the appearance of 1 or more new lesion, if a participant did not have an event at the analysis cut-off date, PFS was censored at the date of the last adequate tumour assessment. Flatiron:PFS=time from the index date to either the date of first PD event or death in the absence of progression; participants without PD or death were censored at the last date the participant could have been assessed for progression or the data analysis cut-off date, whichever occurred first. Index date was =the date of treatment initiation. | Analysis population included all eligible participants whose data were retrieved and observed in this study. | Posted | Median | 95% Confidence Interval | Months | COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months) |
|
|
|
|
| 159 |
| 275 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Dabrafenib+Trametinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 09-January-2014 to 30-September-2021 and treated with Dabrafenib 150 mg BID+ Trametinib 2 mg QD (DAB+TRAM) were included. | 259 | 387 | 0 | 0 | 0 | 0 |
| EG002 | Vemurafenib + Cobimetinib | Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 10-November-2015 to 30-September-2021 and treated with Vemurafenib 960 mg BID+ Cobimetinib 60 mg QD (VEM+COBI) were included. | 30 | 54 | 0 | 0 | 0 | 0 |
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Statistical analysis data is presented for Vemurafenib + Cobimetinib relative to Encorafenib+Binimetinib (reference). |
| Wald Chi- Square Statistic |
| 0.40 |
| Hazard Ratio (HR) |
| 1.20 |
| 2-Sided |
| 95 |
| 0.79 |
| 1.82 |
HR was estimated using multivariable Cox proportional hazard models. |
| Other |